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Biomedical subjects

G M Jones

Publications and source records attributed to G M Jones.

At least 19 recordsLinked to original sources
PubMed2004

Observation of parity nonconservation in møller scattering.

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV)=[-175+/-30(stat)+/-20(syst)] x 10(-9). This first direct observation of parity nonconservation in Møller scattering leads to a measurement of the electron's weak charge at low energy Q(e)(W)=-0.053+/-0.011. This is consistent with the standard model expectation at the current level of precision: sin((2)theta(W)(M(Z))((-)MS)=0.2293+/-0.0024(stat)+/-0.0016(syst)+/-0.0006(theory).

Journal Article↗
PubMed2003

The 'GO' system--a novel method of microculture for in vitro development of mouse zygotes to the blastocyst stage.

A novel system of in vitro culture termed the 'glass oviduct' or 'GO' culture system is described. Mouse zygotes were cultured in pairs to the blastocyst stage in open-ended 1 microl glass capillaries. 'GO' culture supported the development of significantly more hatching or hatched blastocysts than did a standard microdroplet (10 zygotes per 20 microl) control culture (48.3 versus 3.3%, respectively). 'GO' bslastocysts contained significantly larger populations of cells (92+/-3 versus 75+/-3), and inner cell mass (25+/-1 versus 21+/-1) and trophectoderm (68+/-2 versus 53+/-3) subpopulations, compared with microdroplet-derived blastocysts. Before blastulation, 'GO'-derived morulae were found to contain significantly more cells than microdroplet-derived morulae (27+/-0.7 versus 14+/-0.5). After implantation, 'GO' blastocysts formed fetuses at a similar rate to microdroplet-derived blastocysts (55 versus 62%), but at a lower rate than blastocysts derived in vivo (80%). 'GO'- and microdroplet-derived fetuses were similar in wet weight to each other (0.412 and 0.415 g, respectively) but were heavier than fetuses derived from flushed blastocysts (0.390 g). An additional experiment investigated whether the beneficial effect of 'GO' culture was due to the significantly increased embryo density. Proportions of hatching or hatched blastocysts after 'GO' culture (50%) were higher than after standard microdroplet culture (7.6%), but were not different from culture in high embryo density microdroplets (20 zygotes per 10 microl; 42%). 'GO' blastocysts contained more cells (79.6+/-2.1) than did standard microdroplet-derived blastocysts (68.7+/-2.0), but were similar to high density microdroplet-derived blastocysts (85.8+/-2.7). Similarly, 'GO' blastocysts contained more trophectoderm cells (62.2+/-2.0) than did standard microdroplet-derived blastocysts (52.7+/-1.7), but were similar to the high density microdroplet blastocysts (68.8+/-2.5). Numbers of inner cell mass cells ('GO', standard microdroplet and high density microdroplet culture) were not different from each other (17.4+/-0.5, 16+/-0.5 and 17+/-0.4, respectively). In conclusion, the 'GO' culture system represents an alternative method to the microdroplet system for small numbers of preimplantation embryos, without detriment to implantation potential.

Animals↗
PubMed2002

Q2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a 3He target.

We present data on the inclusive scattering of polarized electrons from a polarized 3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference sigma(1/2)-sigma(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q2 of 0.1-0.9 GeV2.

Journal Article↗
PubMed2002

The effect of extracellular matrix molecules on mouse preimplantation embryo development in vitro.

The extracellular matrix (ECM) molecules, laminin (LN), chondroitin sulfate (CS), fibronectin (FN), hyaluronic acid (HA), mucin (MUC) and heparan sulfate proteoglycan (HS), were investigated as supplements to culture medium to improve the in vitro development of mouse 1-cell zygotes to blastocysts. Development was also compared with that in medium supplemented with bovine serum albumin (BSA) to determine the potential for ECM molecules as suitable alternatives to serum albumin in culture medium. Supplementation of sequential culture media with LN at all concentrations examined failed to result in more than 70% of zygotes developing to blastocysts; therefore, LN was considered unsuitable as a replacement for BSA and was not examined further. The optimal concentration of the remaining ECM molecules was used to supplement sequential culture media and the effect on blastocyst quality was assessed by determining the differential cell numbers of blastocysts grown in BSA-supplemented medium. Development to blastocyst was similar, regardless of the macromolecule used. The number of inner cell mass cells was significantly higher in HS-supplemented medium compared with controls. Trophectoderm cell numbers were similar to control values for all ECM molecules examined except CS for which there were fewer trophectoderm cells. It is concluded that ECM molecules, FN, HA, MUC and HS may be used as substitutes for serum protein supplementation of culture media EG0/G2 for mouse preimplantation embryo development. Heparan sulfate proteoglycan increases inner cell mass numbers and this may be due to interactions with the growth factors fibroblast growth factor 4 (FGF-4) and granulocyte-macrophage colony-stimulating factor.

Animals↗
PubMed2001

Inducible mutagenesis in TEPC 2372, a mouse plasmacytoma cell line that harbors the transgenic shuttle vector lambdaLIZ.

The plasmacytoma cell line, TEPC 2372, was derived from a malignant plasma cell tumor that developed in the peritoneal cavity of a BALB/c mouse that harbored the transgenic shuttle vector for the assessment of mutagenesis in vivo, lambdaLIZ. TEPC 2372 was found to display the typical features of a BALB/c plasmacytoma. It consisted of pleomorphic plasma cells that secreted a monoclonal immunoglobulin (IgG2b/lambda), was initially dependent on the presence of IL-6 to grow in cell culture, contained a hyperdiploid chromosome complement with a tendency to undergo tetraploidization, and harbored a constitutively active c-myc gene by virtue of a T(6;15) chromosomal translocation. TEPC 2372 was further characterized by the ability to respond to in vitro exposure with 4-NQO (4-nitroquinoline-1-oxide), an oxidative model mutagen, with a vigorous dose-dependent increase in mutagenesis that peaked at a 7.85-fold elevation of mutant rates in lambdaLIZ when compared to background mutant rates in untreated controls. Cotreatment with 4-NQO and BSO (buthionine sulfoximine), a glutathione-depleting compound that causes endogenous oxidative stress, resulted in a 9.03-fold increase in the mutant frequency in lambdaLIZ. These results demonstrated that TEPC 2372, the malignant plasma cell counterpart of the lambdaLIZ-based in vivo mutagenesis assay, may be useful as an in vitro reference point for the further elucidation of oxidative mutagenesis in lymphoid tissues.

Animals↗
PubMed2001

Sex ratio and birth weights of infants born as a result of blastocyst transfers compared with early cleavage stage embryo transfers.

OBJECTIVE: To analyze the birth weights and sex ratio of infants born as a result of blastocyst transfer and compare them with data resulting from the transfer of early-cleavage stage embryos. DESIGN: Retrospective analysis. SETTING: Monash IVF (private in vitro fertilization clinic). PATIENTS(S): One hundred twenty-five infertile patients who became pregnant after IVF procedures involving blastocyst transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sex ratio and birth weights of infants born after blastocyst transfer. RESULT(S): The sex ratio of 129.6 for infants born after blastocyst transfer was not significantly different from the sex ratio calculated from data compiled by NPSU for births resulting from early cleavage stage embryo transfers at Monash IVF (100.6) and all other assisted conception units in Australia and New Zealand (97.9). No differences were observed in the combined mean birth weight of male and female infants born as a result of blastocyst transfers and early-cleavage stage embryo transfers. CONCLUSION(S): There is no evidence of abnormal fetal growth or a shift in the sex ratio for infants born as a result of blastocyst transfer when compared with the case of births resulting from early cleavage stage embryo transfers within our unit or all other assisted conception units in Australia and New Zealand.

Birth Weight↗
PubMed2001

Ontogeny of hepatic enzymes involved in serine- and folate-dependent one-carbon metabolism in rabbits.

Serine occupies a central position in folate-dependent, one-carbon metabolism through 5,10-methylenetetrahydrofolate (MTHF) and 5-formyltetrahydrofolate (FTHF). We characterized the ontogeny of the specific activity of key enzymes involved in serine, 5,10-MTHF, and 5-FTHF metabolism: methenyltetrahydrofolate synthetase (MTHFS), MTHF reductase (MTHFR), the glycine cleavage system (GCS), methionine synthase (MS), and serine hydroxymethyltransferase (SHMT) in rabbit liver, placenta, brain, and kidney. In liver, MTHFS activity is low in the fetus (0.36 +/- 0.07 nmol. min(-1). mg protein(-1)), peaks at 3 wk (1.48 +/- 0.50 nmol. min(-1). mg protein(-1)), and then decreases to adult levels (1.13 +/- 0.32 nmol. min(-1). mg protein(-1)). MTHFR activity is highest early in gestation (24.9 +/- 2.4 nmol. h(-1). mg protein(-1)) and declines rapidly by birth (4.7 +/- 1.3 nmol. h(-1). mg protein(-1)). MS is highest during fetal life and declines after birth. Cytosolic SHMT activity does not vary during development, but mitochondrial SHMT peaks at 23 days. GCS activity is high in the fetus and the neonate, declining after weaning. In placenta and brain, all activities are low throughout gestation. Cytosolic and mitochondrial SHMT activities are low in kidney and rise after weaning, whereas MTHFS is low throughout development. These data suggest that the liver is the primary site of activity for these enzymes. Throughout development, there are multiple potential sources for production of 5,10-MTHF, but early in gestation high MTHFR activity and low MTHFS activity could reduce 5,10-MTHF availability.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2001

Forward versus backward walking: transfer of podokinetic adaptation.

We asked whether podokinetic adaptation to walking on a circular treadmill transfers to different forms of locomotion. Subjects were blindfolded and asked to walk straight across the floor, in the forward and backward directions, following podokinetic (PK) stimulation that consisted of 30 min of forward walking-in-place on the perimeter of a disk rotating in the clockwise direction. During both forward and backward walking following forward-walking PK stimulation, subjects involuntarily walked along curved trajectories at angular velocities well above vestibular threshold, although they perceived that they were walking along straight paths. The curved paths of forward and backward walking were indistinguishable from one another. Transfer of PK adaptations acquired during forward walking on the turntable to backward walking trials suggests that the PK system controls general locomotor trajectory. Adaptation of the system thus influences forms of locomotion other than that used during acquisition of the adaptation. This transfer also supports the concept that forward and backward walking are controlled by neural networks that share common elements. An interesting feature of the transfer of PK adaptation is that for both forward and backward walking, subjects turned in a counterclockwise direction. As such, the direction of relative rotation between the trunk and feet was maintained for both forward and backward walking. However, the relationship of the lower extremities to the center of rotation was not preserved. The left limb was the inner leg during PK stimulation and forward walking after adaptation, but the left leg was the outer leg during backward walking. These results suggest that PK adaptation affects general locomotor trajectory via a remodeling of the rotational relationship between the trunk and the feet.

Adaptation, Physiological↗
PubMed2000

Oculomotor responses to on-axis rotational stepping in normal and adaptively altered podokinetic states.

Previous studies investigated adaptive properties of a podokinetic (PK) system that senses and controls angular movement of the trunk relative to the stance foot when walking around a curved trajectory or during rotational stepping on the spot. In particular, after adaptively modifying the PK system by prolonged stepping-in-place over the axis of a horizontally rotating platform, blind-folded subjects could no longer step in place on firm ground. When trying to do so they invariably rotated themselves relative to space without perceiving their rotation, a phenomenon termed podokinetic after-rotation (PKAR). It is well known that normal rotational stepping generates a specifically podokinetic component of compensatory nystagmus which is independent of the VOR. The present study investigated whether during PKAR this podokinetic component of oculomotor activity follows the somatosensory correlate of actually stepping around, or the cognitive intent or percept of 'no rotation'. Experiments were conducted in two phases on five normal human subjects. In the first phase, the normal passively induced VOR was compared with the combined VOR and PK oculomotor response induced by intentional rotational stepping on the spot. In both cases the angular stimulus was a 2-min rotation at 15 degrees/s. Subtraction of the decaying VOR from the actively induced combined response revealed a constant podokinetic nystagmus with slow-phase velocity gain of about 0.4 maintained throughout this period. The PK and VOR response components appeared to sum linearly. In the second phase, we measured oculomotor activity during PKAR, when the blindfolded subjects involuntarily rotated themselves at around 15 degrees/s while attempting to step-in-place after the podokinetic adaptation procedure noted above. The striking result of the second phase of experiments was that, although an apparently normal decaying VOR was present, the maintained PK component of response was consistently absent, despite an essentially normal physical pattern of rotational stepping. Thus, in the adapted state, non-vestibular oculomotor activity followed the cognitive intent or percept of 'no rotation', rather than the prevailing somatosensory-motor activity of the lower limbs. The finding points to an important cognitive element in this form of oculomotor control.

Adaptation, Physiological↗
PubMed2000

Mechanisms of toxicity, clinical features, and management of diquat poisoning: a review.

USES: Diquat (1,1'-ethylene-2,2'-bipyridilium) is a nonselective bipyridyl herbicide, related structurally to paraquat, which is used both as a contact herbicide and a preharvest desiccant. In comparison to paraquat, diquat is used much less widely in agriculture. MECHANISMS OF TOXICITY: Diquat is a potent redox cycler and is readily converted to a free radical which, in reaction with molecular oxygen, generates superoxide anions and subsequently other redox products. These products can induce lipid peroxidation in cell membranes, and potentially cause cell death. FEATURES: Over the period 1968-1999, only 30 cases of diquat poisoning were reported in detail in the literature, of which 13 (43%) were fatal. Local and systemic effects have been reported following diquat exposure, with systemic features being invariably associated with ingestion. In severe and usually fatal cases, gastrointestinal mucosal ulceration, paralytic ileus, hypovolemic shock, acute renal failure, and coma have been reported. MANAGEMENT: After rapid confirmation of the diagnosis using a qualitative urine test, gut decontamination may be considered in patients who present within 1 hour of a life-threatening ingestion (>6 g). Supportive measures including fluid and electrolyte replacement should then be employed. Although hemofiltration and hemodialysis are of proven value if renal failure supervenes, there is no clinical evidence that hemodialysis or hemoperfusion removes toxicologically significant amounts of diquat, thereby reducing the risk of organ failure and preventing a fatal outcome in severe cases.

Animals↗
PubMed2000

Effect of recombinant human gonadotrophins on human, bovine and murine oocyte meiosis, fertilization and embryonic development in vitro.

The response of murine, bovine and human oocytes to pure recombinant preparations of human follicle stimulating hormone (rFSH) and luteinizing hormone (rLH) for meiotic maturation and subsequent developmental competence in vitro were examined in the present experiments. Maturation of immature bovine oocytes to the metaphase II stage was significantly increased by the addition of 1 IU/ml of rFSH in combination with either 1 IU/ml rLH or 10 IU/ml rLH. Similarly, embryonic development to the blastocyst stage was improved in bovine oocytes treated with a 1:10 combination of rFSH:rLH. However, no significant difference was observed in the number of inner cell mass or trophectoderm cells of the resulting blastocysts. Although the increased maturation to metaphase II was not significant, human embryonic developmental competence was improved by maturing oocytes in the presence of a 1:10 ratio of rFSH:rLH as only those oocytes exposed to a 1:10 ratio of rFSH: rLH during maturation showed normal cleavage patterns beyond day 2. In addition, 1 IU/ml rFSH and 1 IU/ml rLH increased the expression of oocyte proteins in human oocytes. The inclusion of recombinant gonadotrophins, either singly or in combination, had no significant effect on the maturation, fertilization or embryonic development of in-vitro matured mouse oocytes. These data provide support for the responsiveness of human and bovine oocytes to gonadotrophins in vitro and the need to consider variations in the relative concentrations for optimization of oocyte developmental competence.

Animals↗
PubMed2000

Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro.

In all, 143 human embryos obtained 3 days (day 3) after insemination or intracytoplasmic sperm injection (ICSI) were biopsied and a single nucleated cell removed for identification of aneuploidy by fluorescent in-situ hybridization (FISH) for chromosomes X, Y, 13, 16, 18 and 21. Fifty-one per cent of embryos were aneuploid and significantly more aneuploid embryos blocked in further development to morulae and blastocysts than euploid embryos (59 versus 34%; P < 0.001). Chromosomal analysis of the generated blastocysts revealed 40% were aneuploid (16 of 40 generated blastocysts). Re-examination of cells by FISH for the same chromosome probes of the inner cell mass (ICM) of expanded and hatching blastocysts derived from the aneuploid embryos revealed a high incidence of mosaicism of ICM cell lineages that were usually predictable from observations of day 3 single-cell biopsies. These data would not support the hypothesis of a preferential allocation of euploid cells to the ICM and aneuploid cells to the trophectoderm. A high concordance between day 3 aneuploidy diagnosis and ICM cell lineages was observed with trisomies (97%), and multiple complex chromosome numerical abnormalities (100%). A reduced concordance was observed with monosomies (65%) and haploidy (18%). Concomitantly, the proportion of ICM cell lineages was increased in blastocysts whose chromosomal condition was diagnosed as haploid (21%) or with complex numerical abnormalities (50%).

Aneuploidy↗
PubMed2000

Complex podokinetic (PK) response to post-rotational vestibular stimulation.

Recent studies identified an adaptive "Podokinetic" (PK) sensory motor system involved in sensing and controlling spatial orientation during locomotion, by referencing body orientation to the space-stable stance foot. This paper investigates the interaction of vestibular and PK systems by asking blindfolded subjects to 'step-in-place' (i.e. without turning) after exposing them to a unidirectional post-rotational vestibular stimulus. Six of the nine subjects consistently began by vigorously propelling themselves round in the direction of preceding turntable rotation, but notably without any sensation of turning. In all these subjects the speed of this PK-induced rotation progressively declined to zero over about the next 30 sec and then reversed direction with increasing speed for about 50 sec. Thereafter the speed of rotation declined slowly to zero over the next 4 to 5 minutes. Since the PK-generated body rotation presumably feeds back into the vestibular-PK drive, we formulated a closed loop model of the combined system to investigate the complex nature of the behavioral response. The simulated response of this model closely resembled the experimental data, suggesting that there is indeed a functionally closed loop operating between the vestibular and podokinetic systems in natural life.

Adult↗
PubMed1999

Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas.

The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V(L)) and heavy (V(H)) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V(H)-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes.

Amino Acid Sequence↗
PubMed1999

Analysis of vertical fluorescence resonance energy transfer from the surface of a small-diameter sphere.

Fluorescence resonance energy transfer (FRET) measurements have been used to analyze fluorophore separations in a number of varying geometries, including small particles and extended surfaces. This study focuses on the geometry created by a donor extended above the surface of a small sphere (radius < R0), where the acceptors are integrated into the sphere surface. The model of this geometry was based on an amphipathic molecule with its lipophilic region integrated into a detergent micelle and its hydrophilic region extending outward from the micelle surface, where the donor fluorophore is attached to the hydrophilic region of the molecule. Based on random acceptor incorporation into the micelle, a Poisson distribution was used to calculate the distribution of acceptor probes across the micelle population. The model converges to RET on a flat surface when the radius of the micelle exceeds 0.8 R0. The model was also used to simulate FRET data showing that the positions of donors above the micelle surface could be uniquely resolved. Experimental verification of the model was achieved in a sulfobetaine palmitate micelle with fluorescein isothiocyanate donors attached to detergent-solubilized lipopolysaccharide (LPS) and lipophilic Fast-DiI acceptors. The use of steady-state analysis allowed resolution of cases in which donors were located at different distances from the surface. Combining steady-state with excited-state lifetime analysis allowed resolution of cases where there was a combination of distances. Given the large number of biomolecules that interact with lipids, this approach may prove generally useful for defining molecular conformation.

Biophysical Phenomena↗
PubMed1998

Factors affecting the success of human blastocyst development and pregnancy following in vitro fertilization and embryo transfer.

OBJECTIVE: To determine the factors affecting blastocyst development and pregnancy after IVF and ET. DESIGN: Retrospective analysis of data arising from a clinical trial. SETTING: Private in vitro fertilization clinic. PATIENT(S): Fifty-six patients aged < or = 40 years, undergoing IVF procedures for infertility, recruited specifically for blastocyst transfer. INTERVENTION(S): All zygotes were cultured to days 5 or 6 after insemination, and one to four of the most advanced blastocysts were transferred to the patient's uterus. MAIN OUTCOME MEASURE(S): Development of zygotes to blastocysts in vitro and pregnancy and implantation rates after ET. RESULT(S): Fifty-one percent of all zygotes developed to blastocysts. Significant positive correlation between the number of blastocysts formed was observed with the number of oocytes, pronuclear zygotes, and eight-cell embryos formed. There was a negative correlation with male factor infertility. By day 5 or 6, 93% of the patients had at least one blastocysts, and the clinical pregnancy rate per transfer was 43% and the implantation per embryo transferred was 25%. No other clinical factor significantly affected the number of blastocysts formed, pregnancy rate, or implantation rate. CONCLUSION(S): The numbers of oocytes, zygotes, and normally developing embryos in culture significantly affects the production of blastocysts in vitro. Male infertility significantly reduces blastocyst production. The number and the quality of the blastocysts transferred significantly influences clinical pregnancy rate.

Adult↗